Clinical characteristics and treatment outcomes in six cases of malignant tenosynovial giant cell tumor: initial experience of molecularly targeted therapy.

Abstract

BACKGROUND:

Although tenosynovial giant cell tumor (TGCT) is classified as a benign tumor, it may undergo malignant transformation and metastasize in extremely rare occasions. High aberrant expression of CSF1 has been implicated in the development of TGCT and recent studies have shown promising activity of several CSF1R inhibitors against benign diffuse-type TGCT; however, little is known about their effects in malignant TGCT.

CASE PRESENTATION:

Information from six consenting patients (3 men, 3 women) with malignant TGCT presenting to Dana-Farber Cancer Institute for initial or subsequent consultation was collected. Median age at initial diagnosis of TGCT was 49.5 years (range 12-55), and median age at diagnosis of malignant TGCT was 50 years (range 34-55). Two patients developed malignant TGCT de novo, while four other cases showed metachronous malignant transformation. All tumors arose in the lower extremities (3 knee, 2 thigh, 1 hip). Five patients underwent surgery for the primary tumors, and four developed local recurrence. All six patients developed lung metastases, and four of five evaluable tumors developed inguinal and pelvic lymph node metastases. All six patients received systemic therapy. Five patients were treated with at least one tyrosine kinase inhibitor with inhibitory activity against CSF1R; however, only one patient showed clinical benefit (SD or PR). Five patients were treated with conventional cytotoxic agents. Doxorubicin-based treatment showed clinical benefit in all four evaluable patients, and gemcitabine/docetaxel showed clinical benefit in two patients. All six patients died of disease after a median of 21.5 months from diagnosis of malignant TGCT.

CONCLUSIONS:

This study confirms that TGCT may transform into an aggressive malignant tumor. Lymph node and pulmonary metastases are common. Local recurrence rates are exceedingly high. Conventional cytotoxic chemotherapy showed clinical benefit, whereas tyrosine kinase inhibitors against CSF1R showed limited activity. Given its rarity, a prospective registry of malignant TGCT patients is needed to further understand the entity and to develop effective strategies for systemic treatment.

• Authors: Robert Nakayama, Jyothi Priya Jagannathan, Nikhil Ramaiya, Marco L Ferrone, Chandrajit P Raut, John E Ready, Jason L Hornick, Andrew J Wagner
• Journal: BMC cancer (BMC Cancer) Vol. 18 Issue 1 Pg. 1296 (Dec 29 2018) ISSN: 1471-2407 [Electronic] England
• PMID: 30594158 (Publication Type: Case Reports, Journal Article)

Chemical References

• CSF1R protein, human
• Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Female
• Giant Cell Tumor of Tendon Sheath (drug therapy, pathology, surgery)
• Humans
• Lung Neoplasms (drug therapy, secondary)
• Lymphatic Metastasis (pathology)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Neoplasm Recurrence, Local (drug therapy)
• Receptors, Granulocyte-Macrophage Colony-Stimulating Factor (antagonists & inhibitors)
• Treatment Outcome